Is serotonin in enteric nerves required for distension-evoked peristalsis and propulsion of content in guinea-pig distal colon?

Sia, TC; Flack, Nicholas; Robinson, Lucy; Kyloh, Melinda; Nicholas, Sarah; Brookes, Simon Jonathan; Wattchow, David; Dinning, Phil G.; Oliver, James M.; Spencer, Nick J.

doi:10.1016/j.neuroscience.2013.02.061

Cited by 35 publications

(53 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, depletion of 5-HT in the enteric neurons and removal of the mucosa only partially reduce colonic motility and initiation of the peristaltic reflex (19,41). Thus multiple pathways initiate peristalsis, and loss of one does not preclude initiation of peristalsis and fecal pellet expulsion by the others.…”

Section: Discussionmentioning

confidence: 99%

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

Kendig

Hurst

Bradley

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Kendig DM, Hurst NR, Bradley ZL, Mahavadi S, Kuemmerle JF, Lyall V, DeSimone J, Murthy KS, Grider JR. Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon. Am J Physiol Gastrointest Liver Physiol 307: G1100 -G1107, 2014. First published October 16, 2014; doi:10.1152/ajpgi.00251.2014.-Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5=-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1 Ϫ/Ϫ mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by L-cysteine, but not L-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or L-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. monosodium glutamate, T1R1/T1R3; motility; human colon; chemosensation THE ABILITY OF INTRALUMINAL nutrients to affect motility of the gastrointestinal (GI) tract has been known for decades (14). However, some of the receptors responsible for sensing intraluminal nutrients have only been discovered very recently. These receptors are the same as those responsible for the detection of taste qualities in the lingual epithelium. Multiple studies show the presence of taste receptors and the associated intracellular signaling molecules in the upper GI tract; however, there is less evidence for the existence of these receptors in the distal gut, specifically, the distal colon (13,37,48). While absorption of nutrients occurs almost completely in the small intestine, amino acids from the diet, dead mucosal cells, digested luminal enzymes, and amino acids generated by bacteria are present in the lumin...

show abstract

Section: Discussionmentioning

confidence: 99%

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

Kendig

Hurst

Bradley

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Similar findings have been reported in mice with genetic mutations to block synthesis of mucosally derived 5-HT (42). On the basis of recent findings, it seems more likely that endogenous 5-HT plays a modulatory, but clearly not an essential, role in intestinal motility.While endogenous 5-HT is not required for peristalsis (17,32,34) in vitro or gastrointestinal transit in vivo (42), it is clear from earlier work that nicotinic receptor activation is essential for peristalsis (5, 6). This is highly consistent with the major role of fast nicotinic synaptic potentials recorded from most myenteric neurons (40,41).…”

mentioning

confidence: 99%

Peristalsis and propulsion of colonic content can occur after blockade of major neuroneuronal and neuromuscular transmitters in isolated guinea pig colon

Sia

Brookes

Dinning

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

We recently identified hexamethonium-resistant peristalsis in the guinea pig colon. We showed that, following acute blockade of nicotinic receptors, peristalsis recovers, leading to normal propagation velocities of fecal pellets along the colon. This raises the fundamental question: what mechanisms underlie hexamethonium-resistant peristalsis? We investigated whether blockade of the major receptors that underlie excitatory neuromuscular transmission is required for hexamethonium-resistant peristalsis. Video imaging of colonic wall movements was used to make spatiotemporal maps and determine the velocity of peristalsis. Propagation of artificial fecal pellets in the guinea pig distal colon was studied in hexamethonium, atropine, ω-conotoxin (GVIA), ibodutant (MEN-15596), and TTX. Hexamethonium and ibodutant alone did not retard peristalsis. In contrast, ω-conotoxin abolished peristalsis in some preparations and reduced the velocity of propagation in all remaining specimens. Peristalsis could still occur in some animals in the presence of hexamethonium + atropine + ibodutant + ω-conotoxin. Peristalsis never occurred in the presence of TTX. The major finding of the current study is the unexpected observation that peristalsis can occur after blockade of the major excitatory neuroneuronal and neuromuscular transmitters. Also, the colon retained an intrinsic polarity in the presence of these antagonists and was only able to expel pellets in an aboral direction. The nature of the mechanism(s)/neurotransmitter(s) that generate(s) peristalsis and facilitate(s) natural fecal pellet propulsion, after blockade of major excitatory neurotransmitters, at the neuroneuronal and neuromuscular junction remains to be identified.

show abstract

“…150 As a matter of fact, reserpine has been consistently used to study the characteristics of the releasable pool of 5-HT and other amines. 150,152,153 Other groups reported they found that 5-HT 3 and 5-HT 4 antagonists inhibited CMMCs and pellet propulsion in their reserpinized animals, 19,139,149 however, since the releasable pool of 5-HT was likely to be still intact it seems somewhat presumptive to postulate a non-neuronal 5-HT independent mechanism of these antagonists.…”

Section: Why Are Colonic Migrating Motor Complexes Generated In the Amentioning

confidence: 99%

“…It has recently been proposed that neither neuronal nor mucosal 5-HT are important for fecal pellet propulsion or spontaneous CMMCs, since these were unaffected by reserpine pretreatment, which purportedly depleted all 5-HT from the colon. 19,139,149 Reserpine does not affect the synthesis of 5-HT by TPH but inhibits the vesicular monoamine transporter (reviewed in 8 ); it does however deplete the brain of over 80% of its 5-HT 150 and appears to deplete myenteric ganglia of 5-HT. 33,139 Moreover, it has been known since the 1980s that nerve varicosities have several vesicle compartments for a particular neurotransmitter;…”

Section: Why Are Colonic Migrating Motor Complexes Generated In the Amentioning

confidence: 99%

Colonic Migrating Motor Complexes, High Amplitude Propagating Contractions, Neural Reflexes and the Importance of Neuronal and Mucosal Serotonin

Smith¹,

Park²,

Hennig³

2014

J Neurogastroenterol Motil

View full text Add to dashboard Cite

Is serotonin in enteric nerves required for distension-evoked peristalsis and propulsion of content in guinea-pig distal colon?

Cited by 35 publications

References 24 publications

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

Peristalsis and propulsion of colonic content can occur after blockade of major neuroneuronal and neuromuscular transmitters in isolated guinea pig colon

Colonic Migrating Motor Complexes, High Amplitude Propagating Contractions, Neural Reflexes and the Importance of Neuronal and Mucosal Serotonin

Contact Info

Product

Resources

About